Nitric oxide stimulates ACTH secretion and the transcription of the genes encoding for NGFI-B, corticotropin-releasing factor, corticotropin-releasing factor receptor type 1, and vasopressin in the hypothalamus of the intact rat
Nitric oxide stimulates ACTH secretion and the transcription of the genes encoding for NGFI-B, corticotropin-releasing factor, corticotropin-releasing factor receptor type 1, and vasopressin in the hypothalamus of the intact rat
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DOI：
10.1523/jneurosci.19-17-07640.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
Rivier, C
中科院分区：
文献类型：
--
作者：
Lee, S;Kim, CK;Rivier, C
我们研究了脑室内注射一氧化氮（NO）供体3 - 吗啉代 - 斯德酮亚胺（SIN - 1）对促肾上腺皮质激素（ACTH）释放以及负责此释放的下丘脑神经元的神经元反应的影响。给予SIN - 1的大鼠血浆ACTH水平显著升高，这种反应被抗促肾上腺皮质激素释放因子（CRF）抗体几乎完全消除，并且被血管加压素（VP）抗血清显著减弱。SIN - 1还上调了下丘脑室旁核（PVN）小细胞部分的CRF和VP的异核（hn）转录本以及即早基因NGFI - B和CRF受体1型（CRF - R - 1）的信使RNA（mRNA）水平。用布洛芬阻断前列腺素合成并没有改变ACTH或PVN对SIN - 1的反应。杏仁核中央核和视上核，这些参与心血管活动改变的自主调节的区域，也对SIN - 1有反应，表现为NGFI - B mRNA水平升高。然而，这种NO供体引起的平均动脉血压的唯一变化是短暂且适度的升高。据我们所知，这是首次证明在完整大鼠中NO刺激控制下丘脑 - 垂体 - 肾上腺轴的PVN神经元的活性。然而，必须指出的是，我们的结果不允许我们确定这种影响是直接的还是通过PVN传入神经介导的。这项研究应该有助于解决因使用分离的脑组织来研究NO对下丘脑肽产生的净效应而产生的争议。
We investigated the effect of the intracerebroventricular injection of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) on the release of adrenocorticotropin hormone (ACTH) and the neuronal response of hypothalamic neurons responsible for this release. Rats that were administered SIN-1 showed significant elevations in plasma ACTH levels, a response that was virtually abolished by antibodies against corticotropin-releasing factor (CRF) and significantly blunted by vasopressin (VP) antiserum. SIN-1 also upregulated heteronuclear (hn) transcripts for CRF and VP and messenger RNA (mRNA) levels for the immediate early gene NGFI-B and for CRF receptor type 1 (CRF-R-1) in the parvocellular portion of the paraventricular nucleus (PVN) of the hypothalamus. Blockade of prostaglandin synthesis with ibuprofen did not alter the ACTH or the PVN response to SIN-1. The central nucleus of the amygdala and the supraoptic nucleus, regions that are involved in autonomic adjustments to altered cardiovascular activity, also responded to SIN-1 with elevated NGFI-B mRNA levels. However, the only change in mean arterial blood pressure caused by this NO donor was a transient and modest increase. To our knowledge, this is the first demonstration that in the intact rat NO stimulates the activity of PVN neurons that control the hypothalamic-pituitary-adrenal axis. It must be noted, however, that our results do not allow us to determine whether this effect was direct or mediated through PVN afferents. This study should help resolve the controversy generated by the use of isolated brain tissues to investigate the net effect of NO on hypothalamic peptide production.